Corin

Corin is an enzyme found in most vertebrates.

It is a membrane-bound serine protease of the heart that the peptide hormone atrial natriuretic peptide (ANP ) is activated. Corin is involved in blood pressure regulation. A lack of Corin may possibly lead to arterial hypertension and thus to pressure-related heart disease.

The natriuretic peptide system

Natriuretic peptide endocrine system is a system, which is involved in the regulation of the electrolyte and fluid balance. The system consists of three members of a similar structure: Atrial natriuretic peptide ( ANP), brain natriuretic peptide (BNP ) and C -Type Natriuretic Peptide ( CNP). ANP and BNP are synthesized mainly in the heart, among other CNP in the brain, kidneys, bones and blood vessels. ANP and BNP regulate blood volume and blood pressure. With increased blood volume or blood pressure ANP and BNP are released into the bloodstream and lead to kidney and blood vessels to increased excretion of sodium ( natriuresis ) and water ( diuresis ) to a dilation of blood vessels ( vasodilation ), as well as to inhibition of release renin and endothelin, thereby reducing blood volume and blood pressure. CNP inhibits cell growth of smooth muscle cells and inhibits in animal experiments a narrowing of the coronary arteries.

The natriuretic peptides are synthesized as inactive prohormones. By a signal, the signal peptide is cleaved from the respective pre-pro peptide at first, there arises the propeptide. The propeptide is in the pro-peptide is cleaved by a convertase inactive N-terminal peptide and the biologically active C-terminal peptide.

Corin specifically cleaves pro-ANP to ANP is lesser extent also able to cleave pro-BNP.

The cardiac serine protease Corin

Corin is a membrane-bound serine protease expressed in cardiac muscle cells.

Corin consists of an N -terminal transmembrane domain, two frizzled -like domains, eight LDL receptor repeats, a scavenger receptor domain, and a trypsin proteases similar domain. Corin consists of 1042 amino acids and is a very large protein. Corin has a molecular mass of about 150-200 kDa and has 19 glycosylation sites on. The human Corin gene is one of the largest known protease genes. It is Chromonsom 4p12 -13 with 22 exons and an expansion of more than 200 kilobases.

Corin is mainly formed in the cardiac muscle cell, the expression of Corin m-RNA is in the muscles of the atria than in the ventricles. Low levels of corin mRNA was also found in kidney, bone, and hair follicles. In other muscle rich tissues such as stomach, small intestine, bladder, skeletal muscle and non- pregnant uterus corin mRNA, however, was not detected.

Corin cleaves pro- ANP to ANP. Knockout mice, which lack the corin gene in cardiac muscle tissue forming proANP but no ANP. If the knockout mice Corin fed, they are able to convert pro- ANP in ANP. Corin may also pro- BNP split, although less efficient than pro- ANP. However Pro CNP is not cleaved by corin. The activation pathway of Pro CNP differs from the activation of the ANP and BNP, CNP that is activated in the cell ( intracellular), ANP and BNP, however, at the cell membrane ( extracellularly ).

Animal data

Corin knockout mice develop a high blood pressure, in particular with increased saline supply. In the non- pregnant uterus no Corin m- RNA is detectable in the pregnant uterus on the other hand, large amounts of Corin are detectable. Pregnant Corin knockout mice develop pregnancy-induced hypertension and proteinuria, a condition that is similar to a pre-eclampsia.

Corin variants in humans

So far, two variants in the Corin gene were ( single nucleotide polymorphisms SNP ) () described that among Americans of black African descent frequently ( about 12 % ) than in Caucasians (< 0.2%).

Carriers of the gene variant Corin gene variant I555/P568 have an increased risk of arterial hypertension and cardiac enlargement (concentric cardiac hypertrophy).

Swell

  • Qingyu Wu, Ye Olivia Xu - Cai, Shenghan Chen, Wei Wang: Corin: new insights into the natriuretic peptide System. In: Kidney International. 75, No. 2, 2009, pp. 142-6. doi: 10.1038/ki.2008.418. Retrieved on 28 February 2009.
  • Peptidase
Human Genome Organisation MEROPS Hydrolysis Euteleostomi Smooth muscle tissue Base pair Tissue (biology) Caucasian race Digital Object Identifier
202861
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